The number of women suffering from infertility or menstrual pain due to endometriosis or uterine adenomyosis has been increasing.
Current therapeutic agents for endometriosis include danazol and GnRH analogs. The agents can temporally inhibit the proliferation of endometriotic tissues during the treatment by suppressing functions of a hypothalamo-pituitary-ovarian system and reducing an ovarian hormone. At the same time, the agents can make a menstrual pain disappear by inducing an amenorrheic state.
In the treatment by oral administration of danazol or by subcutaneous injection of GnRH analogs, the drugs circulate the entire body and therefore cause systemic side effects. Because of such side effects, in principle, administration for six months or more is prohibited. Further, these drugs do not directly act on the endometriosis cells themselves and there are many cases in which endometriosis recurs after the end of the treatment for six months. Specifically, if the administration is discontinued after the six-month period, secretion of the ovarian hormone starts again, and often, an endometriosis tissue grows due to the hormone's stimulation and the disease recurs.
As described above, the current therapeutic agents for endometriosis are not those which directly act on and cure endometriosis, and the agents only have an action of indirectly delaying temporally the development of endometriosis. Accordingly, it has been desired to develop a new therapeutic method of directly acting on the endometriotic tissues themselves and suppress systemic side effects to zero or a minimum. On the other hand, with respect to uterine adenomyosis, the above therapeutic agents for endometriosis are less effective, and there is now no effective conservative therapy except for total hysterectomy.
In such a circumstance, one of the present inventors has obtained a patent relating to a danazol topical administration preparation in which danazol is carried on a matrix base (Japanese Patent Laid-Open Publication No. 35335/1995 and Japanese Patent No. 2,590,358).
Meanwhile, 3-ethylpyridine has been used as an additive for many products such as food and cigarette. It has been reported that 3-ethylpyridine inhibits the growth of chorioallantoic membrane of chicken (Lin J. et al., Toxicological Sciences, Vol. 69, 217-225 (2002), and G. Melkonian et al., Anat. Embryol., Vol. 208, 109-120 (2004)). However, up to now, it has not been reported that 3-ethylpyridine is effective in treating and preventing of endometriosis or uterine adenomyosis.